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Molecular viral genomics

This research at Otago focuses on the analysis of viral genome sequences. We are using computational tools to undertake detailed analysis of viral genomes, in search of elements that have been retained during viral evolution. These will have been retained as they have important functions. These elements in the viral genome and the roles they have in viral replication are potential antiviral targets.

Overlapping genes in viral genomes

Software has been developed to identify new genes in viral genomes. It has been made available via a web interface and for download. We have analysed and made predictions for over 600 viral sequences. Experimental testing of these predictions has led to novel discoveries for several key viruses (link).

Hepatitis B virus replication

Viruses frequently use unusual regulatory mechanisms to make essential proteins. Commonly these involve translational control or 'recoding' mechanisms. These are potential sites for anti-viral agents. Most of these recoding mechanisms are poorly understood, but these events are usually directed by sequences and structures in the viral RNAs. These signals may be short RNA sequences or more complex structures.

The synthesis of HBV polymerase (P) protein involves a complex process that differs from host cell protein synthesis, and is a potential target for antiviral agents. The P protein translation initiation site (AUG) is preceded by multiple potential initiation sites, to make any P protein these must somehow be bypassed. P protein is essential for HBV maintenance and multiplication.

A new hypothesis for P protein synthesis has been postulated and tested. The study involves testing the expression of reporter constructs containing part of the viral genome in animal cells. This study will identify the key components of this process, and suggests new avenues for treatment of HBV targeted at this mechanism (link).

HBV Regulatory Sequence Database (HBVRegDB)

Research at Otago focuses on the discovery and analysis of elements that have been conserved during viral evolution. For HBV and other hepadnaviruses we have developed a website and resources for scientists studying HBV molecular biology and regulation of gene expression (link).

For more information contact Dr Chris Brown

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